Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella.
Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella.
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DOI：
10.1186/1475-2859-13-80
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发表时间：
2014-06-04
影响因子：
6.4
通讯作者：
Schifferli DM
中科院分区：
文献类型：
--
作者：
Zhang J;De Masi L;John B;Chen W;Schifferli DM
自转运蛋白是分子工程师的宝库，他们修改革兰氏阴性细菌，以便跨两个膜屏障输出或分泌外来蛋白质。一个特别有前途的方向是开发作为抗原展示或分泌系统的自转运蛋白。免疫学家多年来一直使用卵清蛋白作为报告抗原，并开发出复杂的工具来检测对卵清蛋白有反应的特定 T 细胞。尽管表达卵清蛋白的细菌被用来追踪 T 细胞对定植或入侵病原体的反应，但目前卵清蛋白表达的构建体尚未优化。通过将 OVA-CD4 报告表位以多聚体形式展示在沙门氏菌表面并与自转运蛋白 MisL 融合，可以改善 T 辅助细胞对卵清蛋白的激活。通过包含串联体内启动子和两个用于质粒稳定的分离后杀伤系统来优化表达。使用自转运蛋白在细菌表面呈递相关表位重复，结合有利于稳定和有效体内转录的其他技术，优化了向 T 细胞的抗原呈递。多聚表位表面展示技术也将有利于新型沙门氏菌或其他肠杆菌疫苗的开发。
Autotransporter proteins represent a treasure trove for molecular engineers who modify Gram-negative bacteria for the export or secretion of foreign proteins across two membrane barriers. A particularly promising direction is the development of autotransporters as antigen display or secretion systems. Immunologists have been using ovalbumin as a reporter antigen for years and have developed sophisticated tools to detect specific T cells that respond to ovalbumin. Although ovalbumin-expressing bacteria are being used to trace T cell responses to colonizing or invading pathogens, current constructs for ovalbumin presentation have not been optimized. The activation of T helper cells in response to ovalbumin was improved by displaying the OVA-CD4 reporter epitope as a multimer on the surface of Salmonella and fused to the autotransporter MisL. Expression was optimized by including tandem in vivo promoters and two post-segregational killing systems for plasmid stabilization. The use of an autotransporter protein to present relevant epitope repeats on the surface of bacteria, combined with additional techniques favoring stable and efficient in vivo transcription, optimizes antigen presentation to T cells. The technique of multimeric epitope surface display should also benefit the development of new Salmonella or other enterobacterial vaccines.
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影响因子：
3.8
作者：
HONE, D;ATTRIDGE, S;HACKETT, J
通讯作者：
HACKETT, J
影响因子：
3.1
作者：
Loeffler, Daniela I. M.;Schoen, Christoph U.;Pilgrim, Sabine
通讯作者：
Pilgrim, Sabine
DOI：
10.1073/pnas.76.10.4837
发表时间：
1979-01-01
影响因子：
11.1
作者：
ACHTMAN, M;MANNING, PA;HERRLICH, P
通讯作者：
HERRLICH, P
影响因子：
5.5
作者：
Luria-Perez, R.;Cedillo-Barron, L.;Gonzalez-Bonilla, C. R.
通讯作者：
Gonzalez-Bonilla, C. R.
影响因子：
3.8
作者：
MASKELL, DJ;SWEENEY, KJ;DOUGAN, G
通讯作者：
DOUGAN, G